DESCRIPTION: The goal of this proposal is to study the dynamics of Ca++ trafficking through cellular organelles and its relationship to the regulation of exocytosis using a combination of high time resolution patch clamp, capacitance measurements, amperometry, photometry and imaging. This will be done in single cells and adrenal slice preparations. The specific aims are: 1. Dynamics of Ca++ movement into and out of organelles. Specific hypotheses addressed are that organelles play significant roles in Ca++ homeostasis and that chromaffin secretory granules are Ca++ releasing and sequestering organelles. 2. Signaling pathway for regulated exocytosis in epithelia. The hypothesis that a cAMP-dependent pathway controls exocytosis will be tested. 3. Physiology of chromaffin cells. The hypothesis that chromaffin secretion is regulated by paracrine and modulatory actions will be tested.